Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

Supporting Information Expedient Synthesis of α-Substituted Fluoroethenes Samir K. Mandal, Arun K. Ghosh, Rakesh Kumar and Barbara Zajc* Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031

TABLE OF CONTENTS

Information Page General Experimental Methods 5 Synthesis of 2-[(Aryl)methylthio]benzo[d]thiazoles 5 From Halomethyl Arenes: General Procedure 5 2-[(Naphthalen-1-yl)methylthio]benzo[d]thiazole 6 2-[(2-Bromobenzyl)thio]benzo[d]thiazole 6 2-[(4-Nitrobenzyl)thio]benzo[d]thiazole 7 From Hydroxymethyl Arenes: General Procedure 7 2-[(3,4,5-Trimethoxybenzyl)thio]benzo[d]thiazole 7 2-[(1H-Indol-3-yl)methylthio]benzo[d]thiazole 8 Synthesis of tert-Butyl 3-[(benzo[d]thiazol-2-ylthio)methyl]-1H-indole-1-carboxylate 8 Synthesis of 2-[(Aryl)methylsulfonyl]benzo[d]thiazoles 9 Oxidation of 2-[(Aryl)methylthio]benzo[d]thiazoles: General Procedure 9 2-[(Naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (1a) 9 2-[(2-Bromobenzyl)sulfonyl]benzo[d]thiazole (1c) 10 2-[(3,4,5-Trimethoxybenzyl)sulfonyl]benzo[d]thiazole (1d) 10 2-[(4-Nitrobenzyl)sulfonyl]benzo[d]thiazole (1e) 11 tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)methyl]-1H-indole-1-carboxylate (1g) 11 Fluorination of 2-[(Aryl)methylsulfonyl]benzo[d]thiazoles 12 Synthesis of 2a, 2c, 2d, 2e, 2h: General Procedure 12 2-[Fluoro(naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (2a) 12 2-[(2-Bromophenyl)fluoromethylsulfonyl]benzo[d]thiazole (2c) 13 2-[Fluoro(3,4,5-trimethoxyphenyl)methylsulfonyl]benzo[d]thiazole (2d) 13 2-[Fluoro(4-nitrophenyl)methylsulfonyl]benzo[d]thiazole (2e) 14 tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)fluoromethyl]-1H-indole-1-carboxylate (2g) 14 Synthesis of 2-[(EWG)methylthio]benzo[d]thiazoles and 13C NMR listing for 5b and 5e 15 Synthesis of Ethyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate 15 Synthesis of Benzyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate 15 Synthesis of (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(Benzo[d]thiazol-2-ylthio)-2- 16 fluoroacetate (mixture of two diastereomers in a 1.1:1 ratio) Synthesis of Benzyl 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5c) 17 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

Synthesis of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2- 18 fluoroacetate (5d) Synthesis of Diethyl Fluoro(naphthalen-2-yl)methylphosphonate (4) 18 Condensation Reactions of Fluorosulfones 2a-2e and 5a-5e with Paraformaldehyde: General 19 Procedure Method A 19 Method B 20 1-(1-Fluorovinyl)naphthalene (3a) 20 (1-Fluorovinyl)benzene (3b) 20 1-Bromo-2-(1-fluorovinyl)benzene (3c) 21 5-(1-Fluorovinyl)-1,2,3-trimethoxybenzene (3d) 21 1-(1-Fluorovinyl)-4-nitrobenzene (3e) 22 2-(1-Fluorovinyl)naphthalene (3f) 22 tert-Butyl 3-(1-fluorovinyl)-1H-indole-1-carboxylate (3g) 23 4-(1-Fluorovinyl)-2-(thiophen-2-yl)thiazole (3h) 23 (1-Fluorovinylsulfonyl)benzene (6a) 24 Ethyl 2-Fluoroacrylate (6b) 24 Benzyl 2-Fluoroacrylate (6c) 24 (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-Fluoroacrylate (6d) 25 2-Fluoro-N-methoxy-N-methylacrylamide (6e) 25 Reaction of Diethyl Fluoro(phenylsulfonyl)methylphosphonate with Paraformaldehyde 26 Suzuki Coupling of 1-Bromo-2-(1-fluorovinyl)benzene (3c): General Procedure 26 2-(1-Fluorovinyl)-4'-methoxybiphenyl (7) 26 1-[2'-(1-Fluorovinyl)biphenyl-4-yl]ethanone (8) 27 References 28 1H NMR of 2-[(Naphthalen-1-yl)methylthio]benzo[d]thiazole 29 13C NMR of 2-[(Naphthalen-1-yl)methylthio]benzo[d]thiazole 30 1H NMR of 2-[(2-Bromobenzyl)thio]benzo[d]thiazole 31 13C NMR of 2-[(2-Bromobenzyl)thio]benzo[d]thiazole 32 1H NMR of 2-[(3,4,5-Trimethoxybenzyl)thio]benzo[d]thiazole 33 13C NMR of 2-[(3,4,5-Trimethoxybenzyl)thio]benzo[d]thiazole 34 1H NMR of 2-[(4-Nitrobenzyl)thio]benzo[d]thiazole 35 13C NMR of 2-[(4-Nitrobenzyl)thio]benzo[d]thiazole 36 1H NMR of 2-[(1H-Indol-3-yl)methylthio]benzo[d]thiazole 37 13C NMR of 2-[(1H-Indol-3-yl)methylthio]benzo[d]thiazole 38 1H NMR of tert-Butyl 3-[(benzo[d]thiazol-2-ylthio)methyl]-1H-indole-1-carboxylate 39 13C NMR of tert-Butyl 3-[(benzo[d]thiazol-2-ylthio)methyl]-1H-indole-1-carboxylate 40 1H NMR of 2-[(Naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (1a) 41 13C NMR of 2-[(Naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (1a) 42 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

1H NMR of 2-(Benzylsulfonyl)benzo[d]thiazole (1b) 43 13C NMR of 2-(Benzylsulfonyl)benzo[d]thiazole (1b) 44 1H NMR of 2-[(2-Bromobenzyl)sulfonyl]benzo[d]thiazole (1c) 45 13C NMR of 2-[(2-Bromobenzyl)sulfonyl]benzo[d]thiazole (1c) 46 1H NMR of 2-[(3,4,5-Trimethoxybenzyl)sulfonyl]benzo[d]thiazole (1d) 47 13C NMR of 2-[(3,4,5-Trimethoxybenzyl)sulfonyl]benzo[d]thiazole (1d) 48 1H NMR of 2-[(4-Nitrobenzyl)sulfonyl]benzo[d]thiazole (1e) 49 13C NMR of 2-[(4-Nitrobenzyl)sulfonyl]benzo[d]thiazole (1e) 50 1H NMR of 2-[(Naphthalen-2-yl)methylsulfonyl]ben-zo[d]thiazole (1f) 51 1H NMR of tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)methyl]-1H-indole-1-carboxylate (1g) 52 13C NMR of tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)methyl]-1H-indole-1-carboxylate (1g) 53 1H NMR of 2-{[2-(Thiophen-2-yl)thiazol-4-yl]methylsulfonyl}benzo[d]thiazole (1h) 54 1H NMR of 2-[Fluoro(naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (2a) 55 13C NMR of 2-[Fluoro(naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (2a) 56 1H NMR of 2-[Fluoro(phenyl)methylsulfonyl]benzo[d]thiazole (2b) 57 13C NMR of 2-[Fluoro(phenyl)methylsulfonyl]benzo[d]thiazole (2b) 58 1H NMR of 2-[(2-Bromophenyl)fluoromethylsulfonyl]benzo[d]thiazole (2c) 59 13C NMR of 2-[(2-Bromophenyl)fluoromethylsulfonyl]benzo[d]thiazole (2c) 60 1H NMR of 2-[Fluoro(3,4,5-trimethoxyphenyl)methylsulfonyl]benzo[d]thiazole (2d) 61 13C NMR of 2-[Fluoro(3,4,5-trimethoxyphenyl)methylsulfonyl]benzo[d]thiazole (2d) 62 1H NMR of Crude Reaction Mixture, with Major Component 2-[Fluoro(4- 63 nitrophenyl)methylsulfonyl]benzo[d]thiazole (2e) 1H NMR of 2-[Fluoro(naphthalen-2-yl)methylsulfonyl]benzo[d]thiazole (2f) 64 1H NMR of tButyl 3-[(benzo[d]thiazol-2-ylsulfonyl)fluoromethyl]-1H-indole-1-carboxylate (2g) 65 13C NMR of tButyl 3-[(benzo[d]thiazol-2-ylsulfonyl)fluoromethyl]-1H-indole-1-carboxylate (2g) 66 1H NMR of 2-{Fluoro[2-(thiophen-2-yl)thiazol-4-yl]methylsulfonyl}benzo[d]thiazole (2h) 67 1H NMR of 1-(1-Fluorovinyl)naphthalene (3a) 68 13C NMR of 1-(1-Fluorovinyl)naphthalene (3a) 69 1H NMR of (1-Fluorovinyl)benzene (3b) 70 13C NMR of (1-Fluorovinyl)benzene (3b) 71 1H NMR of 1-Bromo-2-(1-fluorovinyl)benzene (3c) 72 13C NMR of 1-Bromo-2-(1-fluorovinyl)benzene (3c) 73 1H NMR of 5-(1-Fluorovinyl)-1,2,3-trimethoxybenzene (3d) 74 13C NMR of 5-(1-Fluorovinyl)-1,2,3-trimethoxybenzene (3d) 75 1H NMR of 1-(1-Fluorovinyl)-4-nitrobenzene (3e) 76 13C NMR of 1-(1-Fluorovinyl)-4-nitrobenzene (3e) 77 1H NMR of 2-(1-Fluorovinyl)naphthalene (3f) 78 13C NMR of 2-(1-Fluorovinyl)naphthalene (3f) 79 1H NMR of tert-Butyl 3-(1-fluorovinyl)-1H-indole-1-carboxylate (3g) 80 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

13C NMR of tert-Butyl 3-(1-fluorovinyl)-1H-indole-1-carboxylate (3g) 81 1H NMR of 4-(1-Fluorovinyl)-2-(thiophen-2-yl)thiazole (3h) 82 13C NMR of 4-(1-Fluorovinyl)-2-(thiophen-2-yl)thiazole (3h) 83 1H NMR of Diethyl Fluoro(phenylsulfonyl)methylphosphonate (4) 84 13C NMR of Diethyl Fluoro(phenylsulfonyl)methylphosphonate (4) 85 1H NMR of 2-[Fluoro(phenylsulfonyl)methylsulfonyl]benzo[d]thiazole (5a) 86 13C NMR of 2-[Fluoro(phenylsulfonyl)methylsulfonyl]benzo[d]thiazole (5a) 87 1H NMR of Ethyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate 88 1H NMR of Ethyl 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5b) 89 13C NMR of Ethyl 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5b) 90 1H NMR of Benzyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate 91 13C NMR of Benzyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate 92 1H NMR of Benzyl 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5c) 93 13C NMR of Benzyl 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5c) 94 1H NMR of (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(Benzo[d]thiazol-2-ylthio)-2- 95 fluoroacetate (mixture of two diastereomers in a 1.1:1 ratio) 13C NMR of (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(Benzo[d]thiazol-2-ylthio)-2- 96 fluoroacetate (mixture of two diastereomers in a 1.1:1 ratio) 1H NMR of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2- 97 fluoroacetate (5d) 13C NMR of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2- 98 fluoroacetate (5d) 1H NMR of 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (5e) 99 13C NMR of 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (5e) 100 1H NMR of (1-Fluorovinylsulfonyl)benzene (6a) 101 13C NMR of (1-Fluorovinylsulfonyl)benzene (6a) 102 1H NMR of Ethyl 2-Fluoroacrylate (6b) 103 1H NMR of Benzyl 2-Fluoroacrylate (6c) 104 13C NMR of Benzyl 2-Fluoroacrylate (6c) 105 1H NMR of (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-Fluoroacrylate (6d) 106 13C NMR of (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-Fluoroacrylate (6d) 107 1H NMR of 2-Fluoro-N-methoxy-N-methylacrylamide (6e) 108 13C NMR of 2-Fluoro-N-methoxy-N-methylacrylamide (6e) 109 1H NMR of 2-(1-Fluorovinyl)-4'-methoxybiphenyl (7) 110 13C NMR of 2-(1-Fluorovinyl)-4'-methoxybiphenyl (7) 111 1H NMR of 1-[2'-(1-Fluorovinyl)biphenyl-4-yl]ethanone (8) 112 13C NMR of 1-[2'-(1-Fluorovinyl)biphenyl-4-yl]ethanone (8) 113 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

GENERAL EXPERIMENTAL METHODS

THF was distilled over LiAlH4, and then over sodium, methylene chloride was distilled over CaH2

powder, and acetone over anhydrous K2CO3. Toluene was distilled over sodium. DMF was obtained from commercial sources and was used without further purification. For reactions, which were performed under a nitrogen atmosphere, glassware was flame dried under vacuum. LDA (2.0 M solution in heptane/THF/EtPh) was obtained from commercial sources. Fluorinating reagent N-fluorobenzenesulfonimide (NFSI) was a gift from Honeywell (Dr. Andrew Poss), but is also commercially available. Thin layer chromatography was typically performed on aluminum foil-backed silica gel plate (200 µm), except for 3h, where glass-backed silica gel plate (250 µm layer thickness) was used. All other reagents were obtained from commercial sources and used 1 without further purification. H NMR spectra were recorded at 500 MHz in CDCl3, DMSO-d6, and are referenced to the residual protonated solvent resonance. 13C NMR spectra were 19 recorded at 125 MHz and were referenced to CDCl3 or DMSO-d6. F NMR spectra were

recorded at 282 MHz using CFCl3 as internal standard. Chemical shifts (δ) are reported in parts per million and coupling constants (J) are in hertz.

SYNTHESIS OF 2-[(ARYL)METHYLTHIO]BENZO[d]THIAZOLES

Synthesis of 2-(benzylthio)benzo[d]thiazole,1 2-[(naphthalen-2-yl)methylthio]benzo[d]thiazole,1 and 2-{[2-(thiophen-2-yl)thiazol-4-yl]methylthio}benzo[d]thiazole1 has previously been reported by us.

FROM HALOMETHYL ARENES: GENERAL PROCEDURE To a solution of halomethyl arene (1 molar equiv) in DMF (5.5 mL per mmol of halomethyl arene), the sodium salt of 2-mercapto-1,3-benzothiazole (1.2 molar equiv) was added. The reaction mixture was stirred overnight at rt (unless stated otherwise), and complete consumption of the starting material was observed by TLC. The reaction mixture was diluted with water and extracted 3 times with ethyl acetate. The combined organic layer was thoroughly washed with

water and finally with brine, dried over anhydrous Na2SO4 and the solvent evaporated under reduced pressure. The products were either used in the next step as crude, or were purified by column chromatography on silica gel (100-200 mesh, for eluting solvent see specific headings) to give the corresponding sulfide. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

2-[(Naphthalen-1-yl)methylthio]benzo[d]thiazole

N S S

Reaction mixture was heated overnight at 60-65 ºC. 1-(Chloromethyl)naphthalene: 2.00 g (11.3 mmol); sodium salt of 2-mercapto-1,3-benzothiazole: 2.57 g (13.6 mmol, 1.2 molar equiv); DMF: 63.0 mL. Yield of 2-[(naphthalen-1-yl)methylthio]benzo[d]thiazole:2 3.45 g (99%, a white solid). 1 Rf (SiO2, 10% EtOAc in hexanes) = 0.46. Crude product was subjected to oxidation. H NMR

(500 MHz, CDCl3): δ 8.17 (d, 1H, J = 7.8 Hz, Ar-H), 7.96 (d, 1H, J = 7.8 Hz, Ar-H), 7.89 (d, 1H, J = 7.8 Hz, Ar-H), 7.83 (d, 1H, J = 7.8 Hz, Ar-H), 7.77 (d, 1H, J = 7.8 Hz, Ar-H), 7.65 (d, 1H, J = 6.8 Hz, Ar-H), 7.59-7.51 (m, 2H, Ar-H), 7.48-7.41 (m, 2H, Ar-H), 7.32 (t, 1H, J = 7.3 Hz, Ar-H), 13 5.13 (s, 2H, CH2). C NMR (125 MHz, CDCl3): δ 166.7, 153.3, 135.5, 134.1, 131.7, 131.5, 129.1 (2 C), 128.3, 126.7, 126.24, 126.18, 125.6, 124.5, 123.8, 121.7, 121.2, 35.8.

2-[(2-Bromobenzyl)thio]benzo[d]thiazole Br

N S S

1-Bromo-2-(bromomethyl)benzene: 2.00 g (8.00 mmol); sodium salt of 2-mercapto-1,3- benzothiazole: 1.81 g (9.58 mmol, 1.2 molar equiv); DMF: 44.0 mL. Yield of 2-[(2- 3 bromobenzyl)thio]benzo[d]thiazole: 2.60 g (97%, a white). Rf (SiO2, 10% EtOAc in hexanes) = 1 0.49. Crude product was subjected to oxidation. H NMR (500 MHz, CDCl3): δ 7.92 (d, 1H, J = 8.1 Hz, Ar-H), 7.75 (d, 1H, J = 8.1 Hz, Ar-H), 7.62 (d, 1H, J = 7.5 Hz, Ar-H), 7.59 (d, 1H, J = 8.0 Hz, Ar-H), 7.43 (t, 1H, J = 7.5 Hz, Ar-H), 7.30 (t, 1H, J = 8.0 Hz, Ar-H), 7.25 (t, 1H, J = 7.5 Hz, 13 Ar-H), 7.14 (td, 1H, J = 7.5; 1.5 Hz, Ar-H), 4.75 (s, 2H, CH2). C NMR (125 MHz, CDCl3): δ 166.2, 153.3, 136.3, 135.7, 133.2, 131.6, 129.6, 127.9, 126.3, 125.0, 124.5, 121.8, 121.2, 38.1. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

2-[(4-Nitrobenzyl)thio]benzo[d]thiazole

NO2

N S S

1-(Bromomethyl)-4-nitrobenzene: 2.16 g (10.0 mmol); sodium salt of 2-mercapto-1,3- benzothiazole: 2.27 g (12.0 mmol, 1.2 molar equiv); DMF: 55.0 mL. Purification by column 4 chromatography, CH2Cl2 eluting solvent. Yield of 2-[(4-nitrobenzyl)thio]benzo[d]thiazole: 2.75 g 1 (91%, a yellowish solid). Rf (SiO2, 10% EtOAc in hexanes) = 0.36. H NMR (500 MHz, CDCl3): δ 8.18 (d, 2H, J = 8.3 Hz, Ar-H), 7.89 (d, 1H, J = 7.8 Hz, Ar-H), 7.76 (d, 1H, J = 7.8 Hz, Ar-H), 7.65 (d, 2H, J = 8.3 Hz, Ar-H), 7.44 (t, 1H, J = 7.8 Hz, Ar-H), 7.32 (t, 1H, J = 7.8 Hz, Ar-H), 4.67 13 (s, 2H, CH2). C NMR (125 MHz, CDCl3): δ 165.0, 153.1, 147.5, 144.7, 135.7, 130.2 (2C), 126.4, 124.8, 124.0 (2C), 121.8, 121.3, 36.6.

FROM HYDROXYMETHYL ARENES: GENERAL PROCEDURE A solution of 2-mercaptobenzothiazole (1.80 g, 10.8 mmol, 1.2 molar equiv) and diethyl azodicarboxylate (1.88 g, 10.8 mmol, 1.2 molar equiv) in THF (40 mL) was added slowly to a

well stirred solution of hydroxymethyl arene (9 mmol) and PPh3 (2.83 g, 10.8 mmol, 1.2 molar equiv) in THF (10 mL) at 0 ºC. The mixture was stirred for another 15 min at 0 ºC, then warmed to rt and stirred for 6 h. The reaction mixture was concentrated and purified by column chromatography on silica gel (100-200 mesh) using 20% EtOAc in hexanes to give the corresponding sulfide.

2-[(3,4,5-Trimethoxybenzyl)thio]benzo[d]thiazole OMe OMe

S N OMe S

(3,4,5-Trimethoxyphenyl)methanol: 1.78 g (9.0 mmol). Yield of 2-[(3,4,5- 5 trimethoxybenzyl)thio]benzo[d]thiazole: 3.10 g (99%, a colorless liquid). Rf (SiO2, 20% EtOAc 1 in hexanes) = 0.27. H NMR (500 MHz, CDCl3): δ 7.90 (d, 1H, J = 8.3 Hz, Ar-H), 7.76 (d, 1H, J = 7.8 Hz, Ar-H), 7.43 (t, 1H, J = 7.8 Hz, Ar-H), 7.31 (t, 1H, J = 7.8 Hz, Ar-H), 6.70 (s, 2H, Ar-H), 13 4.55 (s, 2H, CH2), 3.84 (s, 6H, OCH3), 3.83 (s, 3H, OCH3). C NMR (125 MHz, CDCl3): δ Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

166.4, 153.5 (2C), 153.3, 135.6, 131.9 (2C), 126.3, 124.6, 121.6, 121.3, 106.4 (2C), 61.0, 56.3 (2C), 38.4.

2-[(1H-Indol-3-yl)methylthio]benzo[d]thiazole NH N S S

(1H-Indol-3-yl)methanol: 1 . 3 3 g ( 9 . 0 m m o l ) . Y i e l d o f 2-[(1H-indol-3- 6 yl)methylthio]benzo[d]thiazole: 2.56 g (96%, a light yellow viscous liquid). Rf (SiO2, 20% EtOAc 1 in hexanes) = 0.24. H NMR (500 MHz, CDCl3): δ 8.15 (br s, 1H, NH), 7.93 (d, 1H, J = 8.0 Hz, Ar-H), 7.75 (t, 2H, J = 7.1 Hz, Ar-H), 7.44 (t, 1H, J = 7.2 Hz, Ar-H), 7.37 (d, 1H, J = 8.0 Hz, Ar- H), 7.32-7.29 (m, 2H, Ar-H), 7.24 (t, 1H, J = 7.5 Hz, Ar-H), 7.18 (t, 1H, J = 7.3 Hz, Ar-H), 4.86 (s, 13 2H, CH2). C NMR (125 MHz, CDCl3): δ 167.6, 153.3, 136.3, 135.4, 126.8, 126.2, 124.3 (2C), 122.7, 121.5, 121.2, 120.1, 119.1, 111.6, 110.2, 29.6.

Synthesis of tert-Butyl 3-[(benzo[d]thiazol-2-ylthio)methyl]-1H-indole-1-carboxylate Boc N N S S

Di-tert-butyl dicarbonate (1.22 g, 5.58 mmol) was added to a well-stirred solution of 2-[(1H-indol- 3-yl)methylthio]benzo[d]thiazole (1.10 g, 3.71 mmol) and DMAP (46.0 mg, 0.377 mmol) in dry acetonitrile (19.0 mL) at rt and the reaction mixture was allowed to stir for 2 h. After completion of the reaction, solvent was removed under reduced pressure and the residue was purified by column chromatography using 10% EtOAc in hexanes to afford tert-butyl 3-[(benzo[d]thiazol-2-

ylthio)methyl]-1H-indole-1-carboxylate (1.37 g, 93%, a white solid). Rf (SiO2, 10% EtOAc in 1 hexanes) = 0.28. H NMR (500 MHz, CDCl3): δ 8.15 (br d, 1H, Ar-H), 7.93 (d, 1H, J = 7.8 Hz, Ar-H), 7.76 (d, 1H, J = 8.3 Hz, Ar-H), 7.71 (s, 1H, Ar-H), 7.68 (d, 1H, J = 7.8 Hz, Ar-H), 7.44 (td, 13 1H, J = 7.7; 1.0 Hz, Ar-H), 7.37-7.28 (m, 3H, Ar-H), 4.77 (s, 2H, CH2), 1.66 (s, 9H, 3CH3). C

NMR (125 MHz, CDCl3): δ 166.4, 153.3, 149.5, 135.6, 135.4, 129.5, 126.1, 125.4, 124.9, 124.4, 122.9, 121.6, 121.1, 119.3, 115.5, 115.2, 83.9, 28.4, 28.3 (3C). HRMS (ESI) calcd for

C21H21N2O2S2 [M + H]+ 397.1039, found 397.1032. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

SYNTHESIS OF 2-[(ARYL)METHYLSULFONYL]BENZO[d]THIAZOLES Synthesis of 2-(benzylsulfonyl)benzo[d]thiazole (1b),1 2-[(naphthalen-2-yl)methylsulfonyl]ben- zo[d]thiazole (1f),1 and 2-{[2-(thiophen-2-yl)thiazol-4-yl]methylsulfonyl}benzo[d]thiazole (1h)1 has previously been reported by us.

OXIDATION OF 2-[(ARYL)METHYLTHIO]BENZO[d]THIAZOLES: GENERAL PROCEDURE

To a vigorously stirred solution of sulfide (1 mmol) in CHCl3 (3.0 mL per mmol of sulfide) at –10 ºC (ice-salt cooling) a solution of m-CPBA (either 70%, or purified, 2.5 mmol, 2.5 molar equiv) in

CHCl3 (8.0 mL per mmol of sulfide) was added dropwise. After complete addition, the mixture was stirred for an additional 10 min at –10 ºC, allowed to warm to room temperature and stirred at room temperature for 8 h. The reaction mixture was then poured into saturated aqueous

NaHCO3 and vigorously stirred for 15 min. After layer separation, the aqueous layer was extracted with organic solvent (see specific procedure), and the combined organic layer was

washed with aqueous NaHCO3, water and brine. The organic layer was dried over anhydrous

Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified either by column chromatography on silica gel (100-200 mesh), or by precipitation (see specific procedure). For each product, the amounts of sulfide precursor, reagents, solvent, purification protocol, and product yield are given under the specific compound headings below. Routinely, although the products can be chromatographically purified, use of material obtained by precipitation (providing better yields) proved to be more than adequate.

2-[(Naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (1a)

O O N S S

2-[(Naphthalen-1-yl)methylthio]benzo[d]thiazole (3.45 g, 11.2 mmol); m-CPBA (4.84 g, 28.0

mmol); CHCl3: 124 mL. Extraction solvent in workup: CH2Cl2. Eluting solvent for column 7 chromatography: CH2Cl2. Yield of 2-[(naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (1a): 1 3.18 g (84%, a white solid). Rf (SiO2, 20% EtOAc in hexanes) = 0.42. H NMR (500 MHz,

CDCl3): δ 8.27 (d, 1H, J = 8.3 Hz, Ar-H), 8.06-8.04 (m, 1H, Ar-H), 7.89 (d, 1H, J = 7.8 Hz, Ar-H), 7.86-7.81 (m, 2H, Ar-H), 7.65 (t, 1H, J = 7.4 Hz, Ar-H), 7.56 (t, 1H, J = 7.4 Hz, Ar-H), 7.45-7.43 13 (m, 3H, Ar-H), 7.36 (t, 1H, J = 7.4 Hz, Ar-H), 5.27 (s, 2H, CH2). C NMR (125 MHz, CDCl3): δ 165.5, 152.8, 137.4, 134.0, 132.4, 131.3, 130.5, 128.9, 128.2, 127.8, 127.1, 126.3, 125.6, 125.4, Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

123.8, 122.9,122.4, 58.4.

2-[(2-Bromobenzyl)sulfonyl]benzo[d]thiazole (1c)

O O N S S Br

2-[(2-Bromobenzyl)thio]benzo[d]thiazole: 2.60 g (7.74 mmol); m-CPBA (4.78 g of 70% m-CPBA,

19.4 mmol of m-CPBA, 2.5 molar equiv); CHCl3: 86.0 mL. Extraction solvent in workup: CH2Cl2.

Crude 1c was purified by precipitation from CH2Cl2 solution by addition of hexanes. Yield of 2- 3b [(2-bromobenzyl)sulfonyl]benzo[d]thiazole (1c): 2.81 g (98%, a white solid). Rf (SiO2, 10% 1 EtOAc in hexanes) = 0.11. H NMR (500 MHz, CDCl3): δ 8.25 (dd, 1H, J = 8.5; 1.5 Hz, Ar-H), 7.98 (dd, 1H, J = 7.3; 1.0 Hz, Ar-H), 7.66 (td, 1H, J = 7.7; 1.1 Hz, Ar-H), 7.60 (td, 1H, J = 7.6; 1.0 Hz, Ar-H), 7.53 (dd, 1H, J = 7.8; 1.0 Hz, Ar-H), 7.46 (dd, 1H, J = 7.6; 1.7 Hz, Ar-H), 7.30 (td, 13 1H, J = 7.4; 1.1 Hz, Ar-H), 7.22 (td, 1H, J = 7.8; 1.5 Hz, Ar-H), 5.00 (s, 2H, CH2). C NMR (125

MHz, CDCl3): δ 165.0, 152.9, 137.5, 133.5, 133.3, 131.1, 128.3, 128.1, 127.9, 127.1, 126.3, + 125.8, 122.5, 60.7. HRMS (ESI) calcd for C14H11BrNO2S2 [M + H] 369.9388, found 369.9393.

2-[(3,4,5-Trimethoxybenzyl)sulfonyl]benzo[d]thiazole (1d) OMe OMe O O S N OMe S

2-[(3,4,5-Trimethoxybenzyl)thio]benzo[d]thiazole: 3.10 g (8.93 mmol); m-CPBA (5.49 g of 70%

m-CPBA, 22.3 mmol of m-CPBA, 2.5 molar equiv); CHCl3: 98.0 mL. Extraction solvent in workup: EtOAc. Eluting solvent for column chromatography: 20% EtOAc in hexanes, followed

by CH2Cl2. Yield of 2-[(3,4,5-trimethoxybenzyl)sulfonyl]benzo[d]thiazole (1d): 3.05 g (90%, a 1 colorless liquid). Rf (SiO2, 10% EtOAc in hexanes) = 0.09. H NMR (500 MHz, CDCl3): δ 8.26 (d, 1H, J = 8.2 Hz, Ar-H), 7.96 (d, 1H, J = 8.2 Hz, Ar-H), 7.65 (t, 1H, J = 8.2 Hz, Ar-H), 7.59 (t,

1H, J = 8.2 Hz, Ar-H), 6.41 (s, 2H, Ar-H), 4.67 (s, 2H, CH2), 3.78 (s, 3H, OCH3), 3.61 (s, 6H, 13 OCH3). C NMR (125 MHz, CDCl3): δ 165.4, 153.4 (2C), 152.6, 138.8, 137.2, 128.2, 127.8,

125.4, 122.5, 121.7, 108.3 (2C), 61.5, 60.9, 56.0 (2C). HRMS (ESI) calcd for C17H17NO5S2Na [M + Na]+ 402.0440, found 402.0446. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

2-[(4-Nitrobenzyl)sulfonyl]benzo[d]thiazole (1e)

NO2 O O N S S

2-[(4-Nitrobenzyl)thio]benzo[d]thiazole: 2.60 g (8.61 mmol); m-CPBA (5.29 g of 70% m-CPBA,

21.5 mmol of m-CPBA, 2.5 molar equiv); CHCl3: 95.0 mL. Extraction solvent in workup: CH2Cl2. Upon solvent concentration, pure product precipitated. Yield of 2-[(4- 8 nitrobenzyl)sulfonyl]benzo[d]thiazole (1e): 2.52 g (88%, a yellowish solid). Rf (SiO2, CH2Cl2) = 1 0.35. H NMR (500 MHz, DMSO-d6): δ 8.30 (t, 2H, J = 7.6 Hz, Ar-H), 8.21 (d, 2H, J = 8.8 Hz, Ar-H), 7.75 (td, 1H, J = 7.8; 1.0 Hz, Ar-H), 7.71 (t, 1H, J = 7.6 Hz, Ar-H), 7.60 (d, 2H, J = 8.7 Hz, 13 Ar-H), 5.35 (s, 2H, CH2). C NMR (125 MHz, DMSO-d6): δ 181.7, 165.3, 152.0, 147.8, 136.5, 134.8, 132.7 (2C), 128.4, 128.2, 125.0, 123.6 (2C), 59.0.

tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)methyl]-1H-indole-1-carboxylate (1g) Boc O O N N S S

tert-Butyl 3-[(benzo[d]thiazol-2-ylthio)methyl]-1H-indole-1-carboxylate: 1.32 g (3.33 mmol); m-

CPBA (2.05 g of 70% m-CPBA, 8.32 mmol of m-CPBA, 2.5 molar equiv); CHCl3: 39.0 mL. Extraction solvent in workup: EtOAc. Eluting solvent for column chromatography: 20% EtOAc in hexanes. Yield of tert-butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)methyl]-1H-indole-1-carboxylate 1 (1g): 0.995 g (70%, a white solid). Rf (SiO2, 20% EtOAc in hexanes) = 0.23. H NMR (500

MHz, CDCl3): δ 8.25 (d, 1H, J = 8.3 Hz, Ar-H), 8.09 (br d, 1H, J = 8.3 Hz, Ar-H), 7.91 (d, 1H, J = 7.8 Hz, Ar-H), 7.64 (td, 1H, J = 7.8; 1.0 Hz, Ar-H), 7.58-7.55 (m, 2H, Ar-H), 7.45 (d, 1H, J = 7.8 Hz, Ar-H), 7.25 (td, 1H, J = 7.8; 1.0 Hz, Ar-H), 7.09 (td, 1H, J = 7.6; 1.0 Hz, Ar-H), 4.92 (s, 2H, 13 CH2), 1.59 (s, 9H, 3 CH3). C NMR (125 MHz, CDCl3): δ 165.4, 152.7, 149.1, 137.2, 135.3, 129.3, 128.1 (2C), 127.8, 125.5, 125.1, 123.1, 122.4, 119.0, 115.3, 106.0, 84.4, 52.4, 28.2 (3C). + HRMS (ESI) calcd for C21H21N2O4S2 [M + H] 429.0937, found 429.0938. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

FLUORINATION OF 2-[(ARYL)METHYLSULFONYL]BENZO[d]THIAZOLES

Synthesis of 2-[fluoro(phenyl)methylsulfonyl]benzo[d]thiazole (2b),1 2-[fluoro(naphthalen-2- yl)methylsulfonyl]benzo[d]thiazole (2f),1 and 2-{fluoro[2-(thiophen-2-yl)thiazol-4- yl]methylsulfonyl}benzo[d]thiazole (2h)1 has previously been reported by us.

SYNTHESIS OF 2a, 2c, 2d, 2e, 2h: GENERAL PROCEDURE A stirred solution of sulfone 1a, 1c, 1d, 1e, 1h (1 molar equiv) in dry toluene (unless stated otherwise, see specific headings, also for the amount), was cooled to –78 ºC (dry-ice/iso-PrOH) under nitrogen. LDA (1.20 molar equiv of a 2 M solution in heptane/THF/EtPh) was added to the reaction mixture. After 20 min solid NFSi (1.20 molar equiv) was added. The mixture was allowed to stir at –78 ºC for 50 min, then warmed to rt and stirring was continued for an

additional 50 min. Sat aq NH4Cl was added to the mixture and the layers were separated. The aqueous layer was extracted with EtOAc (3 x), and the combined organic layer was washed

with sat aq NaHCO3 and brine. The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure. The crude reaction mixtures were purified by column chromatography on 100-200 mesh silica gel. For each substrate, the amount of substrate, reagents and solvent, eluting solvent for chromatography and product yield are given under the specific compound heading below.

2-[Fluoro(naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (2a)

O O N S S F

Sulfone 1a: 0.700 g (2.07 mmol); NFSI: 0.781 g (2.48 mmol); toluene: 70.0 mL; LDA: 1.24 mL (2

M, 2.48 mmol). Eluting solvent for column chromatography: CH2Cl2. Yield of 2a: 0.617 g (84%, 1 a white solid). Rf (SiO2, 20% EtOAc in hexanes) = 0.26. H NMR (500 MHz, CDCl3): δ 8.34 (d, 1H, J = 8.2 Hz, Ar-H), 8.27 (d, 1H, J = 8.5 Hz, Ar-H), 8.04 (t, 2H, J = 7.7 Hz, Ar-H), 7.93 (d, 1H, J = 8.2 Hz, Ar-H), 7.89 (d, 1H, J = 7.2 Hz, Ar-H), 7.70 (td, 1H, J = 7.1; 1.0 Hz, Ar-H), 7.67-7.63 2 13 (m, 2H, Ar-H), 7.60-7.56 (m, 2H, Ar-H), 7.48 (d, 1H, JHF = 45.2 Hz, CHF). C NMR (125 MHz,

CDCl3): δ 163.4, 153.1, 137.8, 133.8, 132.5 (d, JCF = 1.8 Hz), 131.4 (d, JCF = 2.7 Hz), 129.1, 3 2 128.6, 128.5 (d, JCF = 9.6 Hz), 128.1, 127.8, 126.7, 126.0, 125.2, 123.5, 122.55, 122.54 (d, JCF Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

1 19 2 = 17.9 Hz), 99.8 (d, JCF = 220.6 Hz). F NMR (282 MHz, CDCl3): δ –171.58 (d, JHF = 45.7 + Hz). HRMS (ESI) calcd for C18H12FNO2S2Na [M + Na] 380.0186, found 380.0191.

2-[(2-Bromophenyl)fluoromethylsulfonyl]benzo[d]thiazole (2c)

O O N S S F Br

Sulfone 1c: 0.500 g (1.36 mmol); NFSI: 0.513 g (1.63 mmol); toluene: 50 mL; LDA: 0.82 mL (2 M, 1.64 mmol). Eluting solvent for column chromatography: 25% EtOAc in hexanes. Yield of 3b 1 2c: 0.456 g (87%, a white solid). Rf (SiO2, 20% EtOAc in hexanes) = 0.29. H NMR (500

MHz, CDCl3): δ 8.33 (d, 1H, J = 8.3 Hz, Ar-H), 8.06 (d, 1H, J = 7.8 Hz, Ar-H), 7.75 (d, 1H, J = 7.8 Hz, Ar-H), 7.71-7.64 (m, 3H, Ar-H), 7.47 (t, 1H, J = 7.3 Hz, Ar-H), 7.41 (t, 1H, J = 7.6 Hz, Ar- 2 13 H), 7.19 (d, 1H, JHF = 45.4 Hz, CHF). C NMR (125 MHz, CDCl3): δ 162.9, 153.1, 137.8, 3 2 133.7, 133.2, 130.6 (d, JCF = 6.4 Hz), 128.7, 128.1 (2C), 127.0 (d, JCF = 20.6 Hz), 126.1, 124.9 3 1 19 (d, JCF = 4.6 Hz), 122.5, 100.6 (d, JCF = 222.0 Hz). F NMR (282 MHz, CDCl3): δ –170.34 (d, + J = 45.8 Hz). HRMS (ESI) calcd for C14H9FBrNO2S2Na [M + Na] 407.9134, found 407.9137.

2-[Fluoro(3,4,5-trimethoxyphenyl)methylsulfonyl]benzo[d]thiazole (2d) OMe OMe O O S N OMe S F

Sulfone 1d: 1.52 g (4.00 mmol); NFSI: 1.51 g (4.79 mmol); toluene: 160 mL; LDA: 2.40 mL (2 M, 4.80 mmol). Eluting solvent for column chromatography: 35% EtOAc in hexanes. Yield of 2d: 1 1.21 g (76%, a white solid). Rf (SiO2, 30% EtOAc in hexanes) = 0.28. H NMR (500 MHz,

CDCl3): δ 8.30 (d, 1H, J = 8.3 Hz, Ar-H), 8.05 (d, 1H, J = 7.8 Hz, Ar-H), 7.71-7.63 (m, 2H), 6.81 13 (s, 2H, Ar-H), 6.54 (d, 1H, J = 45.4 Hz), 3.88 (s, 3H), 3.85 (s, 6H). C NMR (125 MHz, CDCl3): 2 δ 162.7, 153.5 (2C), 152.7, 140.6, 137.5, 128.4, 127.9, 125.6, 122.3, 121.4 (d, JCF = 20.1 Hz), 3 1 19 105.6 (d, 2C, JCF = 6.4 Hz), 102.2 (d, JCF = 223.8 Hz), 60.8, 56.2 (2C). F NMR (282 MHz, 2 + CDCl3): δ –170.40 (d, JHF = 45.8 Hz). HRMS (ESI) calcd for C17H16FNO5S2Na [M + Na] 420.0346, found 420.0350. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

2-[Fluoro(4-nitrophenyl)methylsulfonyl]benzo[d]thiazole (2e)

NO2 O O N S S F

Sulfone 1e: 1.34 g (4.00 mmol); NFSI: 1.51 g (4.79 mmol); THF:toluene 3:2 (v/v): 160 mL; LDA: 2.40 mL (2 M, 4.80 mmol). Crude reaction mixture: 1.40 g. 2-[Fluoro(4- nitrophenyl)methylsulfonyl]benzo[d]thiazole (2e) could not be separated chromatographically from starting sulfone 1e and difluorinated byproduct 2-[difluoro(4- nitrophenyl)methylsulfonyl]benzo[d]thiazole. Crude reaction mixture was used in the condensation with paraformaldehyde, to give 1-(1-fluorovinyl)-4-nitrobenzene in 71%-78% yield over two steps (depending on the method used, vide infra). 2-[Fluoro(4- 1 nitrophenyl)methylsulfonyl]benzo[d]thiazole (2e): Rf (SiO2, CH2Cl2) = 0.61. H NMR (500 MHz,

CDCl3): δ 8.36 (d, 2H, J = 8.3 Hz), 8.30 (d, 1H, J = 7.8 Hz), 8.07 (d, 1H, J = 7.8 Hz), 7.84 (d, 2H, 19 J = 8.8 Hz), 7.73-7.66 (m, 2H), 6.76 (d, 1H, J = 46.4 Hz). F NMR (282 MHz, CDCl3): δ 2 + –175.59 (d, JHF = 45.8 Hz). HRMS (ESI) calcd for C14H9FN2O4S2Na [M + Na] 374.9880, found 374.9887.

tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)fluoromethyl]-1H-indole-1-carboxylate (2g) Boc O O N N S S F

Sulfone 1g: 0.856 g (2.00 mmol); NFSI: 0.756 g (2.40 mmol); toluene: 60.0 mL; LDA: 1.20 mL (2

M, 2.40 mmol). Eluting solvent for column chromatography: CH2Cl2. Yield of 2g: 0.805 g (90%, 1 a light brownish solid). Rf (SiO2, 20% EtOAc in hexanes) = 0.35. H NMR (500 MHz, CDCl3): δ 8.30 (d, 1H, J = 8.3 Hz, Ar-H), 8.20 (d, 1H, J = 7.8 Hz, Ar-H), 8.05 (d, 1H, J = 7.8 Hz, Ar-H), 8.00 (d, 1H, J = 2.0 Hz, Ar-H), 7.80 (d, 1H, J = 7.8 Hz, Ar-H), 7.70-7.63 (m, 2H, Ar-H), 7.38 (t, 1H, J = 7.8 Hz, Ar-H), 7.28 (t, 1H, J = 8.1 Hz, Ar-H), 6.90 (d, 1H, J = 45.4 Hz), 1.68 (s, 9H). 13C NMR 3 (125 MHz, CDCl3): δ 163.0, 153.0, 148.9, 137.6, 135.6, 129.0 (d, JCF = 8.2 Hz), 128.5, 128.0, 2 1 127.6, 125.8, 125.6, 123.7, 122.4, 120.5, 115.5, 106.9 (d, JCF = 22.4 Hz), 98.7 (d, JCF = 220.2 19 2 Hz), 85.1, 28.2 (3C). F NMR (282 MHz, CDCl3): δ –171.05 (d, JHF = 42.6 Hz). HRMS (ESI) + calcd for C21H19FN2O4S2Na [M + Na] 469.0662, found 469.0675. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

SYNTHESIS OF 2-[(EWG)METHYLTHIO]BENZO[d]THIAZOLES

EWG: ELECTRON WITHDRAWING GROUP

Synthesis of ethyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate9 (synthesis from commercial ethyl bromofluoroacetate also shown below), 2-[fluoro(phenylsulfonyl)methylsulfonyl]benzo[d]thiazole (5a),10 ethyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5b),9 and 2-(benzo[d]thiazol-2- ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (5e)11 has previously been reported by us. We have previously reported the 1H NMR data for 5b and 5e, their 13C NMR data are as follows.

13 2 5b: C NMR (125 MHz, CDCl3): δ 161.3, 160.2 (d, JCF = 24.3 Hz), 152.9, 137.8, 129.0, 128.3, 1 126.2, 122.6, 96.7 (d, JCF = 234.8 Hz), 64.3, 14.1. 13 2 5e: C NMR (125 MHz, CDCl3): δ 161.6, 159.6 (d, JCF = 23.8 Hz), 152.7, 137.9, 128.8, 128.1, 1 126.1, 122.5, 94.8 (d, JCF = 226.1 Hz), 62.2, 32.9.

Synthesis of Ethyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate9 O N S O S F

To a solution of ethyl bromofluoroacetate (1.00 g, 5.41 mmol) in DMF (21.0 mL) at rt, the sodium salt of 2-mercapto-1,3-benzothiazole (1.22 g, 6.49 mmol) was added and the reaction mixture was allowed to stir until complete consumption of the starting material was observed by TLC (within 1 hr). The reaction mixture was diluted with water and extracted with EtOAc (3 x 150 mL). The combined organic layer was thoroughly washed with water, brine, dried over

anhydrous Na2SO4 and the solvent was evaporated under reduced pressure to get crude product that was purified by column chromatography using 25% ethyl acetate in hexanes as

eluent to get 1.20 g (82%) of ethyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate. Rf (SiO2, 25% EtOAc in hexanes) = 0.43. The spectral data of ethyl 2-(benzo[d]thiazol-2-ylthio)-2- fluoroacetate were in agreement with those previously reported by us.9

Synthesis of Benzyl 2-(Benzo[d]thiazol-2-ylthio)-2-fluoroacetate O N S O Ph S F

Catalytic amount of potassium tert-butoxide (49.6 mg, 0.44 mmol, 0.1 molar equiv) was added Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

to a well stirred solution of ethyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate (1.2 g, 4.43 mmol) and benzyl alcohol (2.39 g, 22.14 mmol, 5 molar equiv) in dry benzene (44.0 mL) at 0 ºC. The stirring was continued at 0 ºC for 10 min then the reaction mixture was allowed to stir at rt for 1h, another 0.1 molar equiv (49.6 mg, 0.44 mmol) of tert-butoxide was added and the stirring was continued for 1 h. The reaction was quenched with 10% HCl (30 mL) and diluted with ethyl

acetate. The organic layer was washed with water and brine, dried over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column

chromatography using 230-400 mesh silica gel and CH2Cl2 as eluent to yield (1.09 g, 73%) of

benzyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate as a low melting colorless solid. Rf (SiO2, 1 CH2Cl2) = 0.51. H NMR (500 MHz, CDCl3): δ 7.96 (br d, 1H, J = 7.9 Hz, Ar-H), 7.80 (br d, 1H, J = 7.9 Hz, Ar-H), 7.47 (td, 1H, J = 7.9; 1.0 Hz, Ar-H), 7.38 (td, 1H, J = 7.9; 1.0 Hz, Ar-H), 7.35- 2 13 7.33 (m, 5H, Ar-H), 6.97 (d, 1H, JHF = 50.7 Hz, CHF), 5.30 (s, 2H, CH2). C NMR (125 MHz, 2 CDCl3): δ 164.9 ( JCF = 27.9 Hz), 159.5, 152.8, 136.4, 134.4, 128.9, 128.8 (2C), 128.7 (2C), 1 19 126.7, 125.5, 122.8, 121.4, 92.0 ( JCF = 236.0 Hz), 68.6. F NMR (282 MHz, CDCl3): δ –161.76 2 + (d, JHF = 51.9 Hz). HRMS (ESI) calcd for C16H13FNO2S2 [M + H] 334.0366, found 334.0369.

Synthesis of (1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(Benzo[d]thiazol-2-ylthio)-2-

fluoroacetate (mixture of two diastereomers in a 1.1:1 ratio)

O N S O

S F Catalytic amount of potassium tert-butoxide (62.0 mg, 0.55 mmol) was added to a well stirred solution of ethyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate (1.00 g, 3.69 mmol) and (–)-menthol (2.90 g, 18.6 mmol) in dry hexanes (15.0 mL) at 0 ºC. The stirring was continued at 0 ºC for 10 min then the reaction mixture was allowed to stir at rt for 1.5 h. The reaction was quenched with water and diluted with diethyl ether. The organic layer was washed with water and brine, dried

over anhydrous Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography using 10% ethyl acetate in hexanes as eluent to yield (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate (1.12 g, 79%, a low melting colorless solid) as a mixture of two diastereomers in a 1.1:1 ratio. 1 Rf (SiO2, 10% EtOAc in hexanes) = 0.43. H NMR (500 MHz, CDCl3): δ 7.98 (d, 1H-both isomers, J = 8.3 Hz, Ar-H), 7.82 (d, 1H-both isomers, J = 7.8 Hz, Ar-H), 7.48 (t, 1H-both isomers, J = 7.8 Hz, Ar-H), 7.39 (t, 1H-both isomers, J = 7.8 Hz, Ar-H), 6.90 (d, 1H-one isomer, Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

2 2 JHF = 51.8 Hz), 6.88 (d, 1H-one isomer, JHF = 51.3 Hz), 4.85-4.78 (m, 1H-both isomers), 2.03- 13 0.68 (menthyl protons, 18 H-both isomers). C NMR (125 MHz, CDCl3; for very close signals, chemical shifts are reported to two decimal points, to differentiate between them): δ 164.6 (d, 2 2 JCF = 27.0 Hz), 164.5 (d, JCF = 27.0 Hz), 159.90, 159.88, 152.9, 136.45, 136.40, 126.70, 1 1 126.68, 125.55, 125.52, 122.9, 121.40, 121.37, 92.3 (d, JCF = 236.6 Hz), 92.2 (d, JCF = 236.6 Hz), 77.88, 77.86, 47.0, 46.9, 40.6, 40.4, 34.19, 34.16, 31.6, 31.5, 26.4, 26.2, 23.5, 23.3, 22.09, 19 2 22.05, 20.88, 20.85, 16.4, 16.2. F NMR (282 MHz, CDCl3): δ –161.04 (d, JHF = 48.8 Hz, one 2 + isomer), –161.22 (d, JHF = 48.8 Hz, one isomer). HRMS (ESI) calcd for C19H25FNO2S2 [M + H] 382.1305, found 382.1311.

Synthesis of Benzyl 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5c) O O O N S O Ph S F

To a vigorously stirred solution of benzyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate (1.00 g,

3.00 mmol) in CHCl3 (9 mL) at –10 ºC (ice-salt cooling) a solution of m-CPBA (3.68 g of 70% m-

CPBA, 15 mmol of m-CPBA, 5 molar equiv) in CHCl3 (26 mL) was added dropwise. After complete addition, the mixture was stirred for an additional 10 min at –10 ºC, allowed to warm to room temperature and stirred at room temperature for 48 h. The reaction mixture was then

poured into saturated aqueous NaHCO3 and vigorously stirred for 15 min. After layer

separation, the aqueous layer was extracted with CHCl3, and the combined organic layer was

washed with aqueous NaHCO3, water and brine. The organic layer was dried over anhydrous

Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh) using dichloromethane to yield

0.962 (88%) of benzyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5c) as a white solid. Rf 1 (SiO2, CH2Cl2) = 0.44. H NMR (500 MHz, CDCl3): δ 8.23 (dd, 1H, J = 8.8; 1.5 Hz, Ar-H), 8.01 (dd, 1H, J = 8.8; 1.5 Hz, Ar-H), 7.68-7.63 (m, 2H, Ar-H), 7.35-7.33 (m, 5H, Ar-H), 6.08 (d, 1H, J 13 2 = 47.3 Hz), 5.34 (s, 2H, CH2). C NMR (125 MHz, CDCl3): δ 161.2, 160.2 ( JCF = 23.3 Hz), 1 152.8, 137.8, 133.8, 129.2, 129.0, 128.9 (2C), 128.8 (2C), 128.3, 126.2, 122.6, 96.7 ( JCF = 19 2 235.7 Hz), 69.6. F NMR (282 MHz, CDCl3): δ –181.83 (d, JHF = 48.8 Hz). HRMS (ESI) calcd + for C16H13FNO4S2 [M + H] 366.0265, found 366.0270. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

Synthesis of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylsulfonyl)- 2-fluoroacetate (5d)

O O O N S O

S F

To a vigorously stirred solution of benzyl 2-(benzo[d]thiazol-2-ylthio)-2-fluoroacetate (1.05 g,

2.76 mmol) in CHCl3 (8.3 mL) at –10 ºC (ice-salt cooling) a solution of m-CPBA (1.70 g of 70%

m-CPBA, 6.89 mmol of m-CPBA, 2.5 molar equiv) in CHCl3 (22.0 mL) was added dropwise. After complete addition, the mixture was stirred for an additional 10 min at –10 ºC, allowed to warm to room temperature and stirred overnight at room temperature. The reaction mixture was

then poured into saturated aqueous NaHCO3 and vigorously stirred for 15 min. After layer

separation, the aqueous layer was extracted with CH2Cl2, and the combined organic layer was

washed with aqueous NaHCO3, water and brine. The organic layer was dried over anhydrous

Na2SO4 and the solvent was evaporated under reduced pressure. The crude product was purified first by column chromatography on silica gel (100-200 mesh) using 10% EtOAc in

hexanes, followed by second column chromatography using CH2Cl2 to yield 0.970 g (85%) of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5d) 1 as a gummy oil, that solidifies to white solid on storage. Rf (SiO2, CH2Cl2) = 0.61. H NMR (500

MHz, CDCl3): δ 8.27 (d, 1H-both isomers, Ar-H, J = 8.3 Hz), 8.05 (d, 1H-both isomers, Ar-H, J = 2 7.8 Hz), 7.70-7.64 (m, 2H-both isomers, Ar-H), 6.07 (d, 1H-one isomer, JHF = 47.4 Hz), 6.01 (d, 2 1H-one isomer, JHF = 47.4 Hz), 4.93-4.87 (m, 1H-both isomers), 2.12-0.71 (menthyl protons, 13 2 18H-both isomers). C NMR (125 MHz, CDCl3): δ 161.6, 161.4, 159.82 (d, JCF = 22.9 Hz), 2 159.78 (d, JCF = 23.3 Hz), 152.84, 152.81, 137.8, 137.7, 128.94, 128.91, 128.22, 128.19, 1 1 126.17, 126.13, 122.6, 96.8 (d, JCF = 236.2 Hz), 96.5 (d, JCF = 234.8 Hz), 79.4, 79.3, 46.8, 46.7, 40.5, 40.2, 34.1, 31.6, 26.3, 25.7, 23.4, 23.1, 22.07, 22.05, 20.9, 20.8, 16.2, 16.0. 19F 2 2 NMR (282 MHz, CDCl3): δ –180.55 (d, JHF = 48.8 Hz, one isomer), –181.82 (d, JHF = 45.8 Hz, + one isomer). HRMS (ESI) calcd for C19H25FNO4S2 [M + H] 414.1204, found 414.1206.

Synthesis of Diethyl Fluoro(naphthalen-2-yl)methylphosphonate (4) F

P(OEt)2 O Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

To a stirring solution of diethyl naphthalen-2-ylmethylphosphonate12 (100.0 mg, 0.359 mmol, 1 molar equiv) in dry tetrahydrofuran (20.0 mL) cooled to –78 °C (dry ice/isopropanol) under nitrogen, LDA (1.2 molar equiv of a 2.0 M solution in heptane/THF/EtPh) was added. After 13 min, solid NFSI (176.0 mg, 0.431 mmol, 1.2 molar equiv) was added. The reaction mixture was allowed to stir at –78 °C for 50 min then warmed to room temperature and the stirring was

continued for an additional 50 min. Saturated aq NH4Cl was added to the reaction mixture and the layers were separated. The aqueous layer was extracted with EtOAc (3 times), and the

combined organic layer was washed with water, saturated aq NaHCO3 and brine. The organic

layer was dried over anhydrous Na2SO4 and the solvent was evaporated under reduced

pressure. The crude reaction mixture was purified by column chromatography (SiO2, mesh 200-300, 40% EtOAc in hexanes) to yield 40.2 mg (38 %) of 4 as light yellow oil (unoptimized 1 procedure). Rf (SiO2, 50% CH2Cl2 in hexanes) = 0.29. H NMR (500 MHz, CDCl3): δ 7.95 (br s, 1H, Ar-H), 7.89-7.84 (m, 3H, Ar-H), 7.60 (d, 1H, Ar-H, J = 8.3 Hz), 7.52-7.50 (m, 2H, Ar-H), 5.86

(dd, 1H, CHF, J = 44.7; 7.8 Hz), 4.19-4.00 (m, 4H, CH2A, CH2B), 1.29 (t, 3H, CH3A, J = 7.4 Hz), 13 2 1.26 (t, 3H, CH3B, J = 6.9 Hz). C NMR (125 MHz, CDCl3): δ 133.8, 133.1, 130.6 (d, JCF = 18.4 Hz), 128.53 (d, J = 1.8 Hz), 128.45, 128.0, 126.9, 126.7, 126.6 (app t, J = 7.8 Hz), 124.2 (app t, 2 2 J = 4.8 Hz), 89.9 (dd, J = 184.2; 170.0 Hz), 64.0 (d, JCP = 6.9 Hz, CH2A), 63.6 (d, JCP = 6.9 Hz, 3 3 19 CH2B), 16.61 (d, JCP = 5.5 Hz, CH3A), 16.58 (d, JCP = 6.0 Hz, CH3B). F NMR (282 MHz, 2 2 CDCl3): δ –200.6 (dd, JFP = 83.9 Hz, JFH = 44.3 Hz). HRMS (ESI) calcd for C15H19FO3P [M + H]+ 297.1050, found 297.1059.

CONDENSATION REACTIONS OF FLUOROSULFONES 2a-2e AND 5a-5e WITH PARAFORMALDEHYDE:

GENERAL PROCEDURE For each substrate, synthesis via one method is shown. The amounts of reactants and solvent, eluting solvent for chromatography, and product yield are given under the specific compound headings below.

Method A: In a 20 mL pressure vial, DBU (1,52 g: 10 mmol, or 0.456 g: 3 mmol, see specific headings) in

freshly distilled CH2Cl2 (6 mL per mmol of sulfone) was added to a well-stirrred solution of fluoro sulfone (1 mmol) and paraformaldehyde (300 mg, 10 mmol, 10 molar equiv) in freshly distilled

CH2Cl2 (4 mL per mmol of sulfone) at room temperature. After stirring overnight, the reaction solvent was concentrated, the reaction mixture was directly loaded on silica gel (100-200 mesh, unless stated otherwise) column and fluorovinyl compound was eluted (for eluent, see specific Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

headings).

Method B: In a 20 mL pressure vial, caesium carbonate (652 mg, 2 mmol, 2 molar equiv) was added to a well-stirrred solution of fluoro sulfone (1 mmol) and paraformaldehyde (300 mg, 10 mmol, 10

molar equiv) in freshly distilled solvent (10 mL, CH2Cl2 or THF, see specific headings) at room temperature. The reaction was allowed to stir overnight, solids were removed by filtering through filtering funnel and the filtrate was concentrated. The fluorovinyl products were isolated by column chromatography (100-200 mesh silica gel, unless stated otherwise); for eluent, see specific headings. For each substrate, synthesis via one method is shown, and the amounts of substrate, reagents and solvent, and product yield are given under the specific compound headings below.

1-(1-Fluorovinyl)naphthalene (3a) F

Method A. 2-[Fluoro(naphthalen-1-yl)methylsulfonyl]benzo[d]thiazole (2a): 286 mg (0.800 mmol); paraformaldehyde: 240 mg (8.00 mmol, 10 molar equiv); DBU: 1.22 g (8.00 mmol, 10

molar equiv); CH2Cl2: 8.0 mL. Eluting solvent: 10% EtOAc in hexanes. Yield of 1-(1- 13 fluorovinyl)naphthalene (3a): 92.0 mg (67%, a colorless liquid). R f (SiO2, 10% EtOAc in 1 hexanes) = 0.60. H NMR (500 MHz, CDCl3): δ 8.21 (d, 1H, J = 8.2 Hz, Ar-H), 7.91-7.87 (m, 2H, Ar-H), 7.62 (d, 1H, J = 7.1 Hz, Ar-H), 7.58-7.51 (m, 2H, Ar-H), 7.46 (t, 1H, J = 7.5 Hz, Ar-H), 13 5.16 (dd, 1H, J = 16.1; 2.9 Hz), 4.89 (dd, 1H, J = 48.1; 2.9 Hz). C NMR (125 MHz, CDCl3): δ 1 2 164.2 (d, JCF = 255.0 Hz), 133.8, 130.9, 130.8 (d, JCF = 26.1 Hz), 130.5 (d, JCF = 1.4 Hz),

128.6, 127.5 (d, JCF = 4.6 Hz), 127.0 (d, JCF = 0.9 Hz), 126.4, 125.7 (d, JCF = 4.1 Hz), 125.1, 2 19 3 95.2 (d, JCF = 22.9 Hz). F NMR (282 MHz, CDCl3): δ –88.2 (dd, JHF = 48.8; 15.3 Hz).

(1-Fluorovinyl)benzene (3b) F Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

Method B. 2-[Fluoro(phenyl)methylsulfonyl]benzo[d]thiazole (2b): 307 mg (1.00 mmol);

paraformaldehyde: 300 mg (10.0 mmol, 10 molar equiv); Cs2CO3: 652 mg (2.00 mmol, 2 molar

equiv); CH2Cl2: 10.0 mL. Eluting solvent: CH2Cl2. Product is volatile and solvent needs to be removed cautiously! Yield of 1-(1-fluorovinyl)benzene (3b):14 105 mg (86%, a colorless liquid). 1 Rf (SiO2, CH2Cl2) = 0.81. H NMR (500 MHz, CDCl3): δ 7.57-7.55 (m, 2H), 7.38-7.37 (m, 3H), 13 5.04 (dd, 1H, J = 49.7; 3.4 Hz), 4.85 (dd, 1H, J = 17.7; 3.4 Hz). C NMR (125 MHz, CDCl3): δ 1 2 3 2 163.2 (d, JCF = 249.5 Hz), 132.2 (d, JCF = 29.3 Hz), 129.6, 128.7, 124.8 (d, JCF = 6.9 Hz), 89.7 (d, JCF = 19 3 22.4 Hz). F NMR (282 MHz, CDCl3): δ –108.47 (dd, JHF = 51.9; 18.3 Hz).

1-Bromo-2-(1-fluorovinyl)benzene (3c) F

Br

Method B. 2-[(2-Bromophenyl)fluoromethylsulfonyl]benzo[d]thiazole (2c): 386 mg (1.00 mmol);

paraformaldehyde: 300 mg (10.0 mmol, 10 molar equiv); Cs2CO3: 652 mg (2.00 mmol, 2 molar

equiv); THF: 10.0 mL. Eluting solvent: CH2Cl2. Yield of 1-bromo-2-(1-fluorovinyl)benzene (3c): 1 109 mg (54%, a colorless liquid). Rf (SiO2, 10% EtOAc in hexanes) = 0.61. H NMR (500 MHz,

CDCl3): δ 7.63 (d, 1H, J = 7.9 Hz, Ar-H), 7.48 (d, 1H, J = 7.6 Hz, Ar-H), 7.33 (t, 1H, J = 7.6 Hz, Ar-H), 7.24 (t, 1H, J = 7.9 Hz, Ar-H), 5.09 (dd, 1H, J = 16.5; 3.3 Hz), 4.97 (dd, 1H, J = 48.4; 3.3 13 1 2 Hz). C NMR (125 MHz, CDCl3): δ 162.1 (d, JCF = 253.6 Hz), 133.9 (d, JCF ~ 29 Hz, partially 3 superimposed with resonance at 133.8), 133.8, 130.9, 130.7 (d, JCF = 4.1 Hz), 127.4, 121.7, 2 19 3 95.8 (d, JCF = 22.0 Hz). F NMR (282 MHz, CDCl3): δ –92.00 (dd, JHF = 48.8; 15.3 Hz). + HRMS (EI) calcd for C8H6FBr M 199.9637, found 199.9647.

5-(1-Fluorovinyl)-1,2,3-trimethoxybenzene (3d) F

MeO OMe OMe Method A. 2-[Fluoro(3,4,5-trimethoxyphenyl)methylsulfonyl]benzo[d]thiazole (2d): 220 mg (0.554 mmol); paraformaldehyde: 166 mg (5.54 mmol, 10 molar equiv); DBU: 842 mg (5.54

mmol, 10 molar equiv); CH2Cl2: 5.5 mL. Eluting solvent: 20% EtOAc in hexanes. Yield of 5-(1-

fluorovinyl)-1,2,3-trimethoxybenzene (3d): 108 mg (92%, an off white solid). Rf (SiO2, CH2Cl2) = Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

1 0.61. H NMR (500 MHz, CDCl3): δ 6.77 (s, 2H, Ar-H), 4.95 (dd, 1H, J = 49.6; 3.4 Hz), 4.82 (dd, 13 1H, JHF= 17.6; 3.4 Hz), 3.89 (s, 6H, OCH3), 3.87 (s, 3H, OCH3). C NMR (125 MHz, CDCl3): δ 1 2 3 162.8 (d, JCF = 249.9 Hz), 153.3 (2C), 139.4, 127.6 (d, JCF = 29.8 Hz), 102.2 (d, 2C, JCF = 7.3 2 19 3 Hz), 89.2 (d, JCF = 22.9 Hz), 61.0, 56.3 (2C). F NMR (282 MHz, CDCl3): δ –107.12 (dd, JHF = + 48.8; 18.3 Hz). HRMS (ESI) calcd for C11H14FO3 [M + H] 213.0921, found 213.0924.

1-(1-Fluorovinyl)-4-nitrobenzene (3e) F

NO2 Method B. Crude reaction mixture of 2-[fluoro(4-nitrophenyl)methylsulfonyl]benzo[d]thiazole (2e, along with starting sulfone 1e and difluorinated byproduct, vide supra): 352 mg (1.00 mmol,

calculated on pure 2e); paraformaldehyde: 300 mg (10.0 mmol, 10 molar equiv); Cs2CO3: 652

mg (2.00 mmol, 2 molar equiv); THF: 10.0 mL. Eluting solvent: CH2Cl2. Yield of 1-(1- fluorovinyl)-4-nitrobenzene (3e):13,15 118 mg (70%, a light yellow solid) over two steps 1 (fluorination and condensation step). Rf (SiO2, CH2Cl2) = 0.87. H NMR (500 MHz, CDCl3): δ 8.24 (d, 2H, J = 8.8 Hz, Ar-H), 7.71 (d, 2H, J = 8.8 Hz, Ar-H), 5.26 (dd, 1H, J = 48.8; 3.9 Hz), 13 1 5.10 (dd, 1H, J = 17.1; 3.9 Hz). C NMR (125 MHz, CDCl3): δ 161.0 (d, JCF = 250.8 Hz), 148.3, 2 3 4 2 138.0 (d, JCF = 29.7 Hz), 125.6 (d, JCF = 7.3 Hz), 124.0 (d, 2C, JCF = 2.3 Hz), 93.9 (d, JCF = 19 3 22.0 Hz). F NMR (282 MHz, CDCl3): δ –108.73 (dd, JHF = 48.8; 18.3 Hz).

2-(1-Fluorovinyl)naphthalene (3f) F

Method A. 2-[Fluoro(naphthalen-2-yl)methylsulfonyl]benzo[d]thiazole (2f): 2.70 g (7.56 mmol); paraformaldehyde: 2.28 g (75.9 mmol, 10 molar equiv); DBU: 3.45 g (22.7 mmol, 3 molar

equiv); CH2Cl2: 76.0 mL (tightly stoppered round bottom flask was used instead of pressure

vial). Eluting solvent: CH2Cl2. Yield of 2-(1-fluorovinyl)naphthalene (3f): 1.20 g (92%, a light 1 yellow solid). Rf (SiO2, CH2Cl2) = 0.97. H NMR (500 MHz, CDCl3): δ 8.05 (s, 1H, Ar-H), 7.88- 7.82 (m, 3H, Ar-H), 7.62 (d, 1H, J = 8.6 Hz, Ar-H), 7.52-7.50 (m, 2H, Ar-H), 5.17 (dd, 1H, J = 13 1 49.8; 3.5 Hz), 4.95 (dd, 1H, J = 18.0; 3.4 Hz). C NMR (125 MHz, CDCl3): δ 163.2 (d, JCF = Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

2 249.9 Hz), 133.8, 133.2, 129.4 (d, JCF = 28.8 Hz), 128.8, 128.5 (d, JCF = 2.3 Hz), 127.9, 127.0, 3 3 2 19 126.8, 124.1 (d, JCF = 7.3 Hz), 122.4 (d, JCF = 6.9 Hz), 90.3 (d, JCF = 22.6 Hz). F NMR (282 3 + MHz, CDCl3): δ –108.64 (dd, JHF = 48.8; 18.3 Hz). HRMS (ESI) calcd for C12H9F M 172.0683, found 172.0683.

tert-Butyl 3-(1-fluorovinyl)-1H-indole-1-carboxylate (3g) F

N Boc Method B. tert-Butyl 3-[(benzo[d]thiazol-2-ylsulfonyl)fluoromethyl]-1H-indole-1-carboxylate (2g):

223 mg (0.500 mmol); paraformaldehyde: 150 mg (5.00 mmol, 10 molar equiv); Cs2CO3: 326

mg (1.00 mmol, 2 molar equiv); THF: 5.0 mL. Eluting solvent: CH2Cl2. Yield of tert-butyl 3-(1-

fluorovinyl)-1H-indole-1-carboxylate (3g): 82.0 mg (63%, a light yellow solid). Rf (SiO2, 10% 1 EtOAc in hexanes) = 0.60. H NMR (500 MHz, CDCl3): δ 8.22 (d, 1H, J = 7.8 Hz, Ar-H), 7.81 (s, 1H, Ar-H), 7.73 (d, 1H, J = 7.8 Hz, Ar-H), 7.38 (t, 1H, J = 7.6 Hz, Ar-H), 7.32 (t, 1H, J = 7.8 Hz, Ar-H), 5.00 (dd, 1H, J = 50.8; 3.4 Hz), 4.97 (dd, 1H, J = 19.5; 3.4 Hz), 1.68 (s, 9H, tert-Bu). 13C 1 3 NMR (125 MHz, CDCl3): δ 158.7 (d, JCF = 245.0 Hz), 149.5, 136.1, 126.7 (d, JCF = 6.4 Hz), 3 2 125.2, 124.8 (d, JCF = 6.0 Hz), 123.6, 120.3 (d, JCF = 1.4 Hz), 115.8, 113.9 (d, JCF = 32.5 Hz), 2 19 3 90.9 (d, JCF = 21.5 Hz), 84.6, 28.4 (3C). F NMR (282 MHz, CDCl3): δ –100.70 (dd, JHF = + 51.9; 18.3 Hz). HRMS (EI) calcd for C15H16FNO2 M 261.1165, found 261.1182.

4-(1-Fluorovinyl)-2-(thiophen-2-yl)thiazole (3h) F S N

S Method B. 2-{Fluoro[2-(thiophen-2-yl)thiazol-4-yl]methylsulfonyl}benzo[d]thiazole (2h): 198 mg

(0.50 mmol); paraformaldehyde: 150 mg (5.00 mmol, 10 molar equiv); Cs2CO3: 326 mg (1.00

mmol, 2 molar equiv); THF: 5.0 mL. Eluting solvent: CH2Cl2. Yield of 4-(1-fluorovinyl)-2- 1 (thiophen-2-yl)thiazole (3h): 88.0 mg (83%, a white solid). Rf (SiO2, CH2Cl2) = 0.66. H NMR

(500 MHz, CDCl3): δ 7.54 (d, 1H, J = 3.6 Hz, Ar-H); 7.42 (d, 1H, J = 4.9 Hz, Ar-H), 7.32 (s, 1H, Ar-H), 7.09 (t, 1H, J = 4.6 Hz, Ar-H), 5.49 (dd, 1H, J = 49.7; 3.0 Hz), 4.97 (dd, 1H, J = 17.1; 3.0 13 1 Hz). C NMR (125 MHz, CDCl3): δ 162.5 (d, JCF = 3.7 Hz), 158.6 (d, JCF = 243.5 Hz), 148.7 (d, 2 2 19 JCF = 40.7 Hz), 136.9, 128.4, 128.1, 127.4, 114.7, 92.1 (d, JCF = 16.9 Hz). F NMR (282 MHz, Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

3 + CDCl3): δ –113.42 (dd, JHF = 48.8; 15.3 Hz). HRMS (ESI-APCI) calcd for C9H7FNS2 [M + H] 211.9998, found 212.0000.

(1-Fluorovinylsulfonyl)benzene (6a) O O S

F

Method B. 2-[Fluoro(phenylsulfonyl)methylsulfonyl]benzo[d]thiazole (5a): 371 mg (1.00 mmol);

paraformaldehyde: 300 mg (10.0 mmol, 10 molar equiv); Cs2CO3: 652 mg (2.00 mmol, 2 molar

equiv); CH2Cl2: 10.0 mL. Eluting solvent: CH2Cl2. Yield of (1-fluorovinylsulfonyl)benzene 10,16 1 (6a): 140 mg (75%, a white solid). Rf (SiO2, CH2Cl2) = 0.73. H NMR (500 MHz, CDCl3): δ 7.97 (d, 2H, J = 7.8 Hz, Ar-H), 7.71 (t, 1H, J = 7.3 Hz, Ar-H), 7.60 (t, 2H, J = 7.8 Hz, Ar-H), 5.87 13 (dd, 1H, J = 42.0; 4.9 Hz), 5.43 (dd, 1H, J = 12.6; 4.7 Hz). C NMR (125 MHz, CDCl3): δ 160.7 1 2 19 (d, JCF = 302.1 Hz), 136.9, 134.9, 129.7 (2C), 129.0 (2C), 100.8 (d, JCF = 9.6 Hz). F NMR 3 (282 MHz, CDCl3): δ –115.6 (dd, JHF = 42.7; 12.2 Hz).

Ethyl 2-Fluoroacrylate (6b) O

O F Method B. Ethyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5b): 303 mg (1.00 mmol);

paraformaldehyde: 300 mg (10.0 mmol, 10 molar equiv); Cs2CO3: 652 mg (2.00 mmol, 2 molar

equiv); CH2Cl2: 10.0 mL. Eluting solvent: CH2Cl2. Product is volatile and solvent needs to be removed cautiously, yield lower due to volatility. Yield of ethyl 2-fluoroacrylate (6b):17 76 mg 1 (64%, a volatile, colorless liquid). Rf (SiO2, CH2Cl2) = 0.72. H NMR (500 MHz, CDCl3): δ 5.67 (dd, 1H, J = 43.5; 3.4 Hz), 5.31 (dd, 1H, J = 13.2; 3.4 Hz), 4.30 (q, 2H, J = 7.2 Hz), 1.34 (t, 3H, J 13 2 1 = 7.1 Hz). C NMR (125 MHz, CDCl3): δ 160.6 (d, JCF = 36.1 Hz), 153.7 (d, JCF = 262.3 Hz), 2 19 3 102.7 (d, JCF = 14.6 Hz), 62.1, 14.3. F NMR (282 MHz, CDCl3): δ –117.72 (d, JHF = 42.7 Hz).

Benzyl 2-Fluoroacrylate (6c) O

Ph O F Method B. Benzyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2-fluoroacetate (5c): 183 mg (0.500 mmol); Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

paraformaldehyde: 150 mg (5.00 mmol, 10 molar equiv); Cs2CO3: 326 mg (1.00 mmol, 2 molar

equiv); CH2Cl2: 5.0 mL. Silica gel: 200-300 mesh; eluting solvent: CH2Cl2. Volatile compound, drying under vacuum decreases yield. Yield of benzyl 2-fluoroacrylate (6c):18 after solvent

evaporation and careful drying under vacuum: 59.0 mg (66%, a volatile, colorless liquid). Rf 1 (SiO2, CH2Cl2) = 0.61. H NMR (500 MHz, CDCl3): δ 7.40-7.35 (m, 5H, Ar-H), 5.71 (dd, 1H, J = 13 43.3; 3.1 Hz), 5.34 (dd, 1H, J = 13.1; 3.4 Hz), 5.28 (s, 2H). C NMR (125 MHz, CDCl3): δ 160.5 2 1 2 ( JCF = 36.6 Hz), 153.5 ( JCF = 262.3 Hz), 135.1, 128.9 (2C), 128.8, 128.6 (2C), 103.2 ( JCF = 19 3 15.1 Hz), 67.7. F NMR (282 MHz, CDCl3): δ –117.50 (dd, JHF = 42.7; 12.2 Hz).

(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-Fluoroacrylate (6d)

O O

F

Method B. (1R ,2S ,5R)-2-Isopropyl-5-methylcyclohexyl 2-(benzo[d]thiazol-2-ylsulfonyl)-2- fluoroacetate (5d): 413 mg (1.00 mmol); paraformaldehyde: 300 mg (10.0 mmol, 10 molar

equiv); Cs2CO3: 652 mg (2.00 mmol, 2 molar equiv); CH2Cl2: 10.0 mL. Eluting solvent: CH2Cl2. Yield of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-fluoroacrylate (6d): 156 mg (68%, a 1 colorless oil). Rf (SiO2, 10% EtOAc in hexanes) = 0.71. H NMR (500 MHz, CDCl3): δ 5.65 (dd, 1H, J = 43.7; 3.2 Hz), 5.30 (dd, 1H, J = 12.9; 3.2 Hz), 4.82 (td, 1H, J = 11.0; 4.4 Hz), 2.05 (br d, 1H, J = 11.7 Hz), 1.86 (hept d, 1H, J = 6.8; 2.4 Hz), 1.70 (br d, 2H, J = 11.2 Hz), 1.54-1.45 (m, 2H), 1.13-1.03 (m, 2H), 0.93-0.85 (m, 7H), 0.78 (d, 3H, J = 6.8 Hz). 13C NMR (125 MHz, 2 1 2 CDCl3): δ 160.2 (d, JCF = 36.2 Hz), 153.9 (d, JCF = 262.7 Hz), 102.4 (d, JCF = 15.1 Hz), 76.5, 19 47.2, 40.8, 34.3, 31.6, 26.6, 23.8, 22.2, 20.8, 16.6. F NMR (282 MHz, CDCl3): δ –117.2 (dd, 3 + JHF = 42.7; 12.2 Hz). HRMS (ESI) calcd for C13H21FO2Na [M + Na] 251.1418, found 251.1421. 25 Optical rotation: [α] D = –75.5˚ (c = 1.00 g/100 mL, MeOH).

2-Fluoro-N-methoxy-N-methylacrylamide (6e) O O N F Method B. 2-(Benzo[d]thiazol-2-ylsulfonyl)-2-fluoro-N-methoxy-N-methylacetamide (5e): 159

mg (0.500 mmol); paraformaldehyde: 150 mg (5.00 mmol, 10 molar equiv); Cs2CO3: 326 mg

(1.00 mmol, 2 molar equiv); CH2Cl2: 5.0 mL. Eluting solvent: CH2Cl2. Product is volatile and Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

solvent needs to be removed cautiously. Yield of 2-fluoro-N-methoxy-N-methylacrylamide (6e): 1 59 mg (89%, a volatile colorless liquid). Rf (SiO2, CH2Cl2) = 0.49. H NMR (500 MHz, CDCl3): δ 5.42 (dd, 1H, J = 46.4; 3.4 Hz), 5.17 (dd, 1H, J = 16.6; 3.4 Hz), 3.74 (s, 3H), 3.25 (s, 3H). 13C 2 1 2 NMR (125 MHz, CDCl3): δ 162.1 (d, JCF = 29.7 Hz), 156.6 (d, JCF = 269.6 Hz), 100.6 (d, JCF = 19 3 15.5 Hz), 61.9, 33.7. F NMR (282 MHz, CDCl3): δ –110.79 (dd, JHF = 45.8; 12.2 Hz). HRMS + (ESI) calcd for C5H9FNO2 [M + H] 134.0612, found 134.0612.

Reaction of Diethyl Fluoro(phenylsulfonyl)methylphosphonate with Paraformaldehyde O O S

F

Method B. Diethyl fluoro(phenylsulfonyl)methylphosphonate: 310 mg (1.00 mmol);

paraformaldehyde: 300 mg (10.0 mmol, 10 molar equiv); Cs2CO3: 652 mg (2.00 mmol, 2 molar

equiv); CH2Cl2: 10.0 mL. Eluting solvent: CH2Cl2. Yield of (1-fluorovinylsulfonyl)benzene (6a):10,16 165 mg (89%) of low-melting, light brown solid.

SUZUKI COUPLING OF 1-BROMO-2-(1-FLUOROVINYL)BENZENE (3c): GENERAL PROCEDURE Into an oven-dried vial, purged with argon, 1-bromo-2-(1-fluorovinyl)benzene (3c), (0.10 mmol), arylboronic acid (0.10 mmol), caesium fluoride (0.30 mmol), tris(dibenzylideneacetone)

dipalladium (Pd2(dba)3, 5 mol%) and 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (10 mol%) were weighed. The mixture was purged again with argon and 1,4-dioxane (0.3 mL, 0.33 M solution of 3c) was added. The reaction mixture was stirred at rt for ca 1 min in order to become homogeneous, and then heated under stirring at 80 °C for 2h. The reaction mixture was diluted with dichloromethane, filtered through celite and the filtrate was concentrated under vacuum. The crude reaction mixture was purified by column chromatography using 100-200 mesh silica gel (for eluting solvent see specific headings). The amounts of substrate, reagents and solvent, and product yield are given under the specific compound headings below.

2-(1-Fluorovinyl)-4'-methoxybiphenyl (7) F

OCH3 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

1-Bromo-2-(1-fluorovinyl)benzene (3c): 20.1 mg (0.1 mmol); 4-methoxyphenylboronic acid: 15.2

mg (0.1 mmol); caesium fluoride: 45.6 mg (0.3 mmol); Pd2(dba)3: 4.6 mg (0.005 mmol, 5 mol%); 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine: 3.9 mg (0.01 mmol, 10 mol%); 1,4- dioxane: 0.3 mL (0.33 M solution of 3c). Eluting solvent for column chromatography: 2% EtOAc in hexanes. Yield of 2-(1-fluorovinyl)-4'-methoxybiphenyl (7): 18.6 mg (82%, a colorless liquid). 1 Rf (SiO2, 5% EtOAc in hexanes) = 0.36. H NMR (500 MHz, CDCl3): δ 7.54 (d, 1H, J = 7.8 Hz, ArH), 7.42 (t, 1H, J = 7.3 Hz, ArH), 7.36-7.31 (m, 4H, ArH), 6.95 (d, 2H, J = 8.8 Hz, ArH), 4.81 (dd, 1H, J = 17.1; 2.9 Hz), 4.48 (dd, 1H, J = 49.3; 2.9 Hz), 3.85 (s, 3H). 13C NMR (125 MHz, 1 2 CDCl3): δ 163.8 (d, JCF = 254.0 Hz), 159.2, 140.6, 133.9, 131.5 (d, JCF = 26.1 Hz), 130.9, 129.9 5 3 (d, 2C, JCF = 1.4 Hz), 129.7 (d, JCF = 0.9 Hz), 129.3 (d, JCF = 5.0 Hz), 127.1, 113.9 (2C), 94.7 2 19 3 (d, JCF = 22.0 Hz), 55.5. F NMR (282 MHz, CDCl3): δ –91.52 (dd, JHF = 46.9; 14.7 Hz). + HRMS (ESI) calcd for C15H14FO [M + H] 229.1023, found 229.1025.

1-[2'-(1-Fluorovinyl)biphenyl-4-yl]ethanone (8) F

COCH3 1-Bromo-2-(1-fluorovinyl)benzene (3c): 20.1 mg (0.1 mmol); 4-acetylphenylboronic acid: 16.4

mg (0.1 mmol); caesium fluoride: 45.6 mg (0.3 mmol); Pd2(dba)3: 4.6 mg (0.005 mmol, 5 mol%); 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine: 3.9 mg (0.01 mmol, 10 mol%); 1,4- dioxane: 0.3 mL (0.33 M solution of 3c). Eluting solvent for column chromatography: trace amounts of unreacted 1-bromo-2-(1-fluorovinyl)benzene (3c) were first eluted with 2% EtOAc in hexanes, product 8 was subsequently eluted with 4% EtOAc in hexanes. Yield of 1-[2'-(1-

fluorovinyl)biphenyl-4-yl]ethanone (8): 14.2 mg (59%, a colorless liquid). Rf (SiO2, 10% EtOAc 1 in hexanes) = 0.29. H NMR (500 MHz, CDCl3): δ 8.00 (d, 2H, J = 8.3 Hz, ArH), 7.57 (d, 1H, J = 7.8 Hz, ArH), 7.52 (d, 2H, J = 8.3 Hz, ArH), 7.46 (t, 1H, J = 7.3 Hz, ArH), 7.41 (t, 1H, J = 7.8 Hz, ArH), 7.33 (d, 1H, J = 7.8 Hz, ArH), 4.82 (dd, 1H, J = 16.6; 2.9 Hz), 4.53 (dd, 1H, J = 48.8; 2.9 13 1 Hz), 2.64 (s, 3H). C NMR (125 MHz, CDCl3): δ 198.0, 163.4 (d, JCF = 254.0 Hz), 146.4, 2 3 139.7, 136.2, 131.5 (d, JCF = 26.1 Hz), 130.6, 129.9 (d, JCF = 0.9 Hz), 129.5 (d, JCF = 4.6 Hz), 2 19 129.0 (d, 2C, JCF = 1.8 Hz), 128.6 (2C), 128.1, 95.1 (d, JCF = 22.9 Hz), 26.9. F NMR (282 3 + MHz, CDCl3): δ –90.89 (dd, JHF = 46.9; 14.7 Hz). HRMS (ESI) calcd for C16H14FO [M + H] 241.1023, found 241.1026. Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

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